PURPOSE: Signal transducers and activators of transcription (STATs)were shown to be activated in mammary carcinoma. Because different STAT factors are likely to have different functions in these tumors, an assessment of their individual role is mandatory. EXPERIMENTAL DESIGN: In this study we have separately determined activation of STAT1, STAT3, and STAT5 by measuring their DNA binding activity and tyrosine phosphorylation in breast cancer tissue samples. The predictive value of STAT activation on relapse-free and overall survival among women who received treatment for primary breast cancer was evaluated in a retrospective study. RESULTS: Survival analysis demonstrated that patients with high STAT1 activation have substantially longer overall and relapse-free survival, irrespective of whether STAT1 activation was determined by its DNA binding activity (P = 0.003 and 0.010, respectively) or by its tyrosine phosphorylation (P = 0.046 and 0.011, respectively). In accordance, Cox proportional hazard regression analysis revealed an enhanced hazard of death (hazard ratio, 3.77; P = 0.018) and relapse of disease (hazard ratio, 6.55; P = 0.013) for the group of women with low STAT1 activation. After adjusting for known prognostic variables (lymph node status, stage of disease, estrogen receptor status, and cathepsin D), STAT1 activation remained an independent prognostic value. Activation of STAT3 and STAT5 DNA binding did not significantly correlate with prognosis. CONCLUSION: Our study reveals a favorable and independent prognostic significance of STAT1 activation in mammary carcinoma, and is in accordance with the documented role of STAT1 in growth arrest, and in pro-apoptotic signaling pathways.
PURPOSE: Signal transducers and activators of transcription (STATs)were shown to be activated in mammary carcinoma. Because different STAT factors are likely to have different functions in these tumors, an assessment of their individual role is mandatory. EXPERIMENTAL DESIGN: In this study we have separately determined activation of STAT1, STAT3, and STAT5 by measuring their DNA binding activity and tyrosine phosphorylation in breast cancer tissue samples. The predictive value of STAT activation on relapse-free and overall survival among women who received treatment for primary breast cancer was evaluated in a retrospective study. RESULTS: Survival analysis demonstrated that patients with high STAT1 activation have substantially longer overall and relapse-free survival, irrespective of whether STAT1 activation was determined by its DNA binding activity (P = 0.003 and 0.010, respectively) or by its tyrosine phosphorylation (P = 0.046 and 0.011, respectively). In accordance, Cox proportional hazard regression analysis revealed an enhanced hazard of death (hazard ratio, 3.77; P = 0.018) and relapse of disease (hazard ratio, 6.55; P = 0.013) for the group of women with low STAT1 activation. After adjusting for known prognostic variables (lymph node status, stage of disease, estrogen receptor status, and cathepsin D), STAT1 activation remained an independent prognostic value. Activation of STAT3 and STAT5 DNA binding did not significantly correlate with prognosis. CONCLUSION: Our study reveals a favorable and independent prognostic significance of STAT1 activation in mammary carcinoma, and is in accordance with the documented role of STAT1 in growth arrest, and in pro-apoptotic signaling pathways.
Authors: Xingxing Liu; Mélanie Nugoli; Julie Laferrière; Sadiq M Saleh; Ian G Rodrigue-Gervais; Maya Saleh; Morag Park; Michael T Hallett; William J Muller; Vincent Giguère Journal: Proc Natl Acad Sci U S A Date: 2010-12-27 Impact factor: 11.205
Authors: Haiyan Yang; Li-Rong Yu; Ming Yi; David A Lucas; Luanne Lukes; Mindy Lancaster; King C Chan; Haleem J Issaq; Robert M Stephens; Thomas P Conrads; Timothy D Veenstra; Kent W Hunter Journal: J Proteome Res Date: 2006-07 Impact factor: 4.466
Authors: Ricardo D Coletta; Paul Jedlicka; Arthur Gutierrez-Hartmann; Heide L Ford Journal: J Mammary Gland Biol Neoplasia Date: 2004-01 Impact factor: 2.673
Authors: Tobias N Dechow; Laura Pedranzini; Andrea Leitch; Kenneth Leslie; William L Gerald; Irina Linkov; Jacqueline F Bromberg Journal: Proc Natl Acad Sci U S A Date: 2004-07-12 Impact factor: 11.205